Abstract
The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arterioles / abnormalities
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Arterioles / growth & development
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Base Sequence
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Body Patterning / genetics
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Body Patterning / physiology
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DNA / genetics
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Endothelial Growth Factors / genetics*
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Endothelial Growth Factors / physiology*
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Female
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Gene Expression Regulation, Developmental
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Gene Targeting
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Lymphokines / genetics*
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Lymphokines / physiology*
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Male
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Mice
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Mice, Transgenic
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Pregnancy
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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Receptor Protein-Tyrosine Kinases / genetics
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Receptors, Growth Factor / genetics
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Receptors, Vascular Endothelial Growth Factor
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Retinal Vessels / abnormalities
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Retinal Vessels / growth & development*
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Venules / abnormalities
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Venules / growth & development
Substances
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Endothelial Growth Factors
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Lymphokines
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Protein Isoforms
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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DNA
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor